Delivery devices for administering a beneficial agent to a biological fluid environment of use are known in the prior art. Representative examples of various types of delivery devices are disclosed in European publications EP 25,699 and 164,241 and in U.S. Pat. Nos. 3,995,632, 4,111,202, 4,251,506, 4,612,008, 4,824,675, 4,865,598, 4,872,873, 4,876,093, 4,892,778, 4,915,949, 4,940,465 and 5,023,088.
While the prior art delivery devices usually work successfully for their intended purpose, it has now been observed that the devices do not function well when the formulation to be dispensed is a hydrophilic beneficial agent formulation, that is, a beneficial agent formulation where the agent is combined with a hydrophilic carrier. When a hydrophilic agent formulation is dispensed from previous devices, uncontrolled release of the agent is often a problem, causing delivery of the agent into the environment of use in amounts and over periods of time that are not intended by the design of the device, and resulting in erratic or incorrect dosage profiles. This has been found to be particularly true in dynamic or vigorous environments such as active, grazing animals. Such uncontrolled release of a hydrophilic formulation has not been recognized or addressed in the prior art.
To overcome the limitations associated with the prior art delivery devices, a delivery device has been developed and is described and claimed in copending, commonly-assigned patent applications U.S. Ser. No. 07/641,023, filed Jan. 11, 1991, and U.S. Ser. No. 07/763,393, filed on Sep. 19, 1991, now U.S. Pat. No. 5,126,142 both to Ayer et al. This delivery device comprises a housing containing a beneficial agent such as an ionophore together with a hydrophilic carrier, an expandable driving member composition, and a densifier, the housing also having an exit passageway or a multiplicity of exit passageways, the diameter of each passageway being of a size to maximize release of the beneficial agent by osmotic pumping and minimize release of the beneficial agent by diffusion or erosion to substantially avoid mechanical agitation-dependent beneficial agent release. The expandable driving member absorbs liquid from the environment of use, expands and acts to drive out beneficial agent formulation from the interior of the device in a controlled manner for a prolonged period of time up to six months or longer.
While the device of U.S. Pat. No. 5,126,142 and No. 07/763,393 functions successfully to provide and maintain a controlled dosage of beneficial agent to the environment of use for an extended period of time, the device has the disadvantage of exhibiting a significant startup time between administration of the device to the subject animal or human and the onset of agent delivery at the desired rate.
Provision of effective dosages upon administration of the device can be obtained by prehydration (i.e., soaking) of the device prior to administration. For example, a device which exhibits a three-week delay prior to onset of effective delivery of the desired agent can be soaked for three weeks prior to administration to the subject. Effective delivery of the desired agent thus begins upon administration. However, prehydration of a long-term device has several significant disadvantages. The soaking of a single device for a period of three weeks requires a processing step which is undesirable, but it is likely to be manageable. However, the soaking of sufficient individual devices with which to supply an entire herd of animals can require a container the size of a swimming pool or a small lake. Also, the active agent which is being delivered by the device is distributed into the water in which the device is soaked, and can require special treatment of the water before it can be released into ground or sewage waters. Additionally, if the device has a limited lifespan (i.e., decomposition of the semipermeable membrane, density means, or other component of the device takes place over time), the time during which the device is prehydrated may limit the effective use in the subject animal.
The teachings of the prior art pertaining to loading doses of beneficial agent regarding short-term delivery devices do not provide a solution to the problem of the startup delay in long-term devices. An example of instantaneous delivery of agent from a short-term device is shown in U.S. Pat. No. 4,643,731, whereby instantaneous concentration of agent is obtained by providing a loading dose, i.e., an initial, immediate, short-term dose of beneficial agent, prior to the onset of the continuous delivery provided by the osmotic pump device. Due to the kinetics of the release of loading doses for short-term devices, the loading doses are active for only a short time and do not sustain the concentration of beneficial agent during the startup period demonstrated by long-term devices. Those loading doses provided within the coating of a short-term device are not appropriate for use with long-term devices having a semipermeable mebrane, as such coatings can interfere with the permeability of the semipermeable membrane and thus interfere with the operation of the device.